RNA aptamers generated against oligomeric Abeta40 recognize common amyloid aptatopes with low specificity but high sensitivity.

Aptamers are useful molecular recognition tools in research, diagnostics, and therapy. Despite promising results in other fields, aptamer use has remained scarce in amyloid research, including Alzheimer's disease (AD). AD is a progressive neurodegenerative disease believed to be caused by neurotoxic amyloid beta-protein (Abeta) oligomers. Abeta oligomers therefore are an attractive target for development of diagnostic and therapeutic reagents. We used covalently-stabilized oligomers of the 40-residue form of Abeta (Abeta40) for aptamer selection. Despite gradually increasing the stringency of selection conditions, the selected aptamers did not recognize Abeta40 oligomers but reacted with fibrils of Abeta40, Abeta42, and several other amyloidogenic proteins. Aptamer reactivity with amyloid fibrils showed some degree of protein-sequence dependency. Significant fibril binding also was found for the naïve library and could not be eliminated by counter-selection using Abeta40 fibrils, suggesting that aptamer binding to amyloid fibrils was RNA-sequence-independent. Aptamer binding depended on fibrillogenesis and showed a lag phase. Interestingly, aptamers detected fibril formation with > or =15-fold higher sensitivity than thioflavin T (ThT), revealing substantial beta-sheet and fibril formation undetected by ThT. The data suggest that under physiologic conditions, aptamers for oligomeric forms of amyloidogenic proteins cannot be selected due to high, non-specific affinity of oligonucleotides for amyloid fibrils. Nevertheless, the high sensitivity, whereby aptamers detect beta-sheet formation, suggests that they can serve as superior amyloid recognition tools

A controlled study of community-based exercise training in patients with moderate COPD.

BackgroundThe effectiveness of clinic-based pulmonary rehabilitation in advanced COPD is well established, but few data exist for less severe patients treated in alternative settings. The purpose of this study was to investigate whether a novel, community-based exercise program (CBE) was feasible and effective for patients with moderate COPD.MethodsNineteen patients with moderate COPD (mean FEV1 62%) and self-reported exercise impairment were randomized to 12-weeks of progressive endurance and strength training at a local health club under the guidance of a certified personal trainer, or to continuation of unsupervised habitual physical activity. Outcomes assessed at baseline and 12 weeks included session compliance, intensity adherence, treadmill endurance time, muscle strength, dyspnea, and health status.ResultsCompliance was 94% and adherence was 83%. Comparisons between CBE and control groups yielded the following mean (SEM) differences in favor of CBE: endurance time 134 (74) seconds versus -59 (49) seconds (P=0.041) and TDI 5.1 (0.8) versus -0.2 (0.5) (P<0.001). The CBE group increased muscle strength (weight lifted) by 11.8 kilograms per subject per week of training (P<0.001). SGRQ was not significantly changed.ConclusionsWe demonstrated the feasibility and effectiveness of a novel community-based exercise program involving health clubs and personal trainers for patients with moderate COPD.Trial registrationClinicalTrials.gov Identifier NCT01985529

Antiferromagnetic Critical Fluctuations in BaFe2_2As2_2

Magnetic correlations near the magneto-structural phase transition in the bilayer iron pnictide parent compound, BaFe$_2$As$_2$, are measured. In close proximity to the antiferromagnetic phase transition in BaFe$_2$As$_2$, a crossover to three dimensional critical behavior is anticipated and has been preliminarily observed. Here we report complementary measurements of two-dimensional magnetic fluctuations over a broad temperature range about T$_N$. The potential role of two-dimensional critical fluctuations in the magnetic phase behavior of BaFe$_2$As$_2$ and their evolution near the anticipated crossover to three dimensional critical behavior and long-range order are discussed.Comment: 6 pages, 4 figures; Accepted for publication in Physical Review

Goal-directed versus outcome-based financial incentives for weight loss among low-income patients with obesity: rationale and design of the Financial Incentives foR Weight Reduction (FIReWoRk) randomised controlled trial.

IntroductionObesity is a major public health challenge and exacerbates economic disparities through employment discrimination and increased personal health expenditures. Financial incentives for weight management may intensify individuals' utilisation of evidence-based behavioural strategies while addressing obesity-related economic disparities in low-income populations. Trials have focused on testing incentives contingent on achieving weight loss outcomes. However, based on social cognitive and self-determination theories, providing incentives for achieving intermediate behavioural goals may be more sustainable than incentivising outcomes if they enhance an individual's skills and self-efficacy for maintaining long-term weight loss. The objective of this paper is to describe the rationale and design of the Financial Incentives foR Weight Reduction study, a randomised controlled trial to test the comparative effectiveness and cost-effectiveness of two financial incentive strategies for weight loss (goal directed vs outcome based) among low-income adults with obesity, as well as compared with the provision of health behaviour change resources alone.Methods and analysisWe are recruiting 795 adults, aged 18-70 years with a body mass index ≥30 kg/m2, from three primary care clinics serving residents of socioeconomically disadvantaged neighbourhoods in New York City and Los Angeles. All participants receive a 1-year commercial weight loss programme membership, self-monitoring tools (bathroom scale, food journal and Fitbit Alta HR), health education and monthly check-in visits. In addition to these resources, those in the two intervention groups can earn up to $750 over 6 months for: (1) participating in an intensive weight management programme, self-monitoring weight and diet and meeting physical activity guidelines (goal-directed arm); or (2) a ≥1.5% to ≥5% reduction in baseline weight (outcome-based arm). To maximise incentive efficacy, we incorporate concepts from behavioural economics, including immediacy of payments and framing feedback to elicit regret aversion. We will use generalised mixed effect models for repeated measures to examine intervention effects on weight at 6, 9 and 12 months.Ethics and disseminationHuman research protection committees at New York University School of Medicine, University of California Los Angeles (UCLA) David Geffen School of Medicine and Olive-View-UCLA Medical Center granted ethics approval. We will disseminate the results of this research via peer-reviewed publications, conference presentations and meetings with stakeholders.Trial registration numberNCT03157713

Copper vapor laser machining of polyimide and polymethylmethacrylate in atmospheric pressure air

A repetitively pulsed copper vapor laser (510 and 578 nm) is used to machine an opaque polymer (polyimide‐Vespel) and a transparent polymer (polymethylmethacrylate‐Lucite). Lucite is machinable by coating the surface with an ink which is semi‐opaque to the green and yellow laser light. The repetition rate of the laser was 10 kHz with approximately 0.35 mJ/pulse and 3.5 W average power at the copper vapor laser wavelengths for a pulse width of 40 ns. The copper vapor laser thermally loads the target, generating thermal waves and sound waves in the gas which are investigated using HeNe laser beam deflection. The gas adjacent to the target is heated to steady state on the order of 100–400 s. Above the etching threshold, at approximately 10 mJ/cm2/pulse, the target is rapidly machined: 2‐mm‐diam, 2‐mm‐deep holes are drilled in 300 s in Vespel. At higher fluences of 100–150 mJ/cm2/pulse in 760 Torr of air it takes 180 s to bore through a 2‐mm‐thick disk of Vespel. The machined surfaces of the two polymers are very different. Machined Vespel samples are charred and cratered, whereas the Lucite samples show evidence of melting with little charring. The machining of polymers by visible‐light copper vapor lasers is being compared to UV photoablation by KrF excimer laser light in order to study thermal versus nonthermal etching mechanisms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71173/2/JAPIAU-72-7-3080-1.pd

Perturbation: the Catastrophe Causer in Scale-Free Networks

A new model about cascading occurrences caused by perturbation is established to search after the mechanism because of which catastrophes in networks occur. We investigate the avalanche dynamics of our model on 2-dimension Euclidean lattices and scale-free networks and find out the avalanche dynamic behaviors is very sensitive to the topological structure of networks. The experiments show that the catastrophes occur much more frequently in scale-free networks than in Euclidean lattices and the greatest catastrophe in scale-free networks is much more serious than that in Euclidean lattices. Further more, we have studied how to reduce the catastrophes' degree, and have schemed out an effective strategy, called targeted safeguard-strategy for scale-free networks.Comment: 4 pages, 6 eps figure

Unbiased optical mapping of telomere-integrated endogenous human herpesvirus 6

Next-generation sequencing technologies allowed sequencing of thousands of genomes. However, there are genomic regions that remain difficult to characterize, including telomeres, centromeres, and other low-complexity regions, as well as transposable elements and endogenous viruses. Human herpesvirus 6A and 6B (HHV-6A and HHV-6B) are closely related viruses that infect most humans and can integrate their genomes into the telomeres of infected cells. Integration also occurs in germ cells, meaning that the virus can be inherited and result in individuals harboring the virus in every cell of their body. The integrated virus can reactivate and cause disease in humans. While it is well established that the virus resides in the telomere region, the integration locus is poorly defined due to the low sequence complexity (TTAGGG)n of telomeres that cannot be easily resolved through sequencing. We therefore employed genome imaging of the integrated HHV-6A and HHV-6B genomes using whole-genome optical site mapping technology. Using this technology, we identified which chromosome arm harbors the virus genome and obtained a high resolution map of the integration loci of multiple patients. Surprisingly, this revealed long telomere sequences at the virus-subtelomere junction that were previously missed using PCR-based approaches. Contrary to what was previously thought, our technique revealed that the telomere lengths of chromosomes harbor ing the integrated virus genome were comparable to the other chromosomes. Taken together, our data shed light on the genetic structure of the HHV-6A and HHV-6B integration locus, demonstrating the utility of optical mapping for the analysis of genomic regions that are difficult to sequence

Desperate housewives: An analysis of the characterisations of female gamblers portrayed in gambling movies in Hong Kong

This article examines portrayals of female gamblers in recent Hong Kong movies. The authors report that the depiction of female gamblers is very different from that of male gamblers in the movies made in the same period. Whereas the male gamblers are pitching a lonely and desperate battle against the evil opponent, the female gamblers portrayed in the movies are housewives or small-time players who gamble only for their personal gain. A general negative overtone in portrayals of female gamblers was interpreted as a reflection of the traditional view that discourages women from gambling. The shift of gambling themes in the Hong Kong movies has been identified to reflect the most salient concerns among Hong Kong residents. Such changes are attributed to particular social and cultural changes in the community